This invention relates to using a change in quantum dot luminescence as a detectable signal in receptor-ligand binding assays. It is a general method for detecting an analyte that is receptor, cognate ligand, or competitors thereof.
Semiconductor quantum dots are inorganic nanoparticles with remarkable photophysical properties.1-5 In particular, their one- and two-photon absorption cross sections, luminescence lifetimes, and photobleaching resistances are significantly greater than those of conventional organic fluorophores. Furthermore, their broad absorption bands extend continuously from the ultra-violet to the visible region of the electromagnetic spectrum and, therefore, offer a vast selection of possible excitation wavelengths. Instead, their narrow emission bands can precisely be positioned within the visible and near-infrared regions with fine adjustments of their physical dimensions. In fact, pools of quantum dots with different diameters can be designed to emit in parallel at different wavelengths after excitation at a single wavelength, offering the opportunity to implement unprecedented multichannel assays.
Organic dyes do not offer the unique collection of attractive photophysical properties associated with semiconductor quantum dots. Indeed, it is becoming apparent that these inorganic nanoparticles can complement, if not replace, their organic counterparts in a diversity of biomedical applications.6-12 Nonetheless, decades of intensive investigations on the structure and properties of organic chromophores have indicated valuable strategies to design sensitive fluorescent probes able to signal the presence of target analytes with changes in emission intensity:13-16 Their operating principles generally rely on the covalent connection of a fluorescent component to a receptor. The receptor is then engineered to quench the emission of the fluorophore on the basis of either electron or energy transfer. The supramolecular association of the receptor with its cognate ligand (e.g., a target analyte), however, suppresses the quenching mechanism and leads to a significant enhancement in fluoresence intensity. Under these conditions, the presence of the target analyte is therefore transduced into a detectable fluorescence signal. In the past, however, it was not entirely clear if and how these strategies could successfully be extended to quantum dots.
Promising studies demonstrated that semiconductor quantum dots can donate energy to complementary partners.17 In fact, clever assays for the recognition of various analytes are starting to be designed on the basis of energy transfer processes.18-30 But the use of reaction mechanisms based on electron transfer in receptor-ligand assays remains to be explored and exploited.31-32 
Therefore, it is an objective of the invention to provide improved compositions for sensing an analyte through receptor-ligand interaction (i.e., binding) and transducing a detectable signal by a change in quantum dot luminescence. Other advantages and improvements are described below or would be apparent from the disclosure herein.